title: Clinical characteristics and outcomes of chédiak-Higashi syndrome: a nationwide survey of Japan.
abstract: BACKGROUND
  Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by immunodeficiency, neurological dysfunction, and oculocutaneous albinism. Recently, several clinical CHS phenotypes have been reported. Here, we report results of a nationwide survey performed to clarify clinical characteristics and outcomes of CHS patients in Japan.
  
  
  METHODS
  Questionnaires were sent to 287 institutions to collect data regarding CHS patients diagnosed between 2000 and 2010, including results of lysosomal trafficking regulator (LYST) gene analysis. Cytotoxicity and degranulation activity of cytotoxic T lymphocytes were analyzed in available patient samples.
  
  
  RESULTS
  A total of 15 patients diagnosed with CHS were eligible for enrollment in this study. Of these, 10 (67%) had recurrent bacterial infections, five (33%) developed life-threatening hemophagocytic lymphohistiocytosis (HLH), and one patient had complicated malignant lymphoma. Hematopoietic stem cell transplantation (HSCT) was performed for six patients including three with HLH, and 10 of the enrolled patients have survived at the time of this writing. LYST analysis was performed for 10 patients; seven different mutations were detected in seven patients, whereas no mutation was identified in three patients. Cytotoxicity and degranulation activity were impaired in patients with and without LYST mutation.
  
  
  CONCLUSIONS
  Results of this survey indicate that one or two patients with CHS were newly diagnosed each year in Japan. The incidence of HLH was not as high as expected. Mutations of genes other than LYST were suspected in some cases. We conclude that determining indication for HSCT for CHS patients should be based on genetic and cytotoxic analysis.
authors.affiliation: Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Nagai
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ochi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.forename: Miho
authors.initials: M
authors.lastname: Maeda
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kitoh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kogawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohta
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishida
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakiguchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
mesh_terms: D000293:Adolescent; D000328:Adult; D002609:Chediak-Higashi Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008223:Lymphoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C102161:LYST protein, human; D033921:Vesicular Transport Proteins
keywords: Chédiak-Higashi syndrome; cytotoxic T lymphocyte; degranulation activity; lysosomal trafficking regulator (LYST) gene